Genetic Variant NM_020921.4:c.5188T>G (chr14-50743529-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020921.4(NIN):c.5188T>G(p.Leu1730Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1730L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NIN
NM_020921.4 missense, splice_region

Scores

Splicing: ADA: 0.0001048

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.528

Publications

0 publications found

Variant links:

Genes affected

NIN (HGNC:14906): (ninein) This gene encodes one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the microtubules minus-ends in epithelial cells. Localization of this protein to the centrosome requires three leucine zippers in the central coiled-coil domain. Multiple alternatively spliced transcript variants that encode different isoforms have been reported. [provided by RefSeq, Jul 2008]

NIN Gene-Disease associations (from GenCC):

Seckel syndrome 7
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

NIN links:

LOC124903313 (HGNC:):

LOC124903313 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14577773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020921.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NIN	NM_020921.4	MANE Select	c.5188T>G	p.Leu1730Val	missense splice_region	Exon 24 of 31	NP_065972.4
NIN	NM_182946.2		c.5188T>G	p.Leu1730Val	missense splice_region	Exon 24 of 30	NP_891991.2
NIN	NM_182944.3		c.5188T>G	p.Leu1730Val	missense splice_region	Exon 24 of 30	NP_891989.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NIN	ENST00000530997.7	TSL:5 MANE Select	c.5188T>G	p.Leu1730Val	missense splice_region	Exon 24 of 31	ENSP00000436092.2
NIN	ENST00000382041.7	TSL:1	c.5188T>G	p.Leu1730Val	missense splice_region	Exon 24 of 30	ENSP00000371472.3
NIN	ENST00000382043.8	TSL:1	c.3049T>G	p.Leu1017Val	missense splice_region	Exon 22 of 28	ENSP00000371474.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454388

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1105378

Other (OTH)

AF:

0.00

AC:

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.031

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.82

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.84

PhyloP100

0.53

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.55

REVEL

Benign

0.17

Sift

Benign

0.39

Sift4G

Benign

1.0

Polyphen

1.0

Vest4

0.13

MutPred

0.11

Gain of methylation at K1729 (P = 0.0486)

MVP

0.60

MPC

0.14

ClinPred

0.057

GERP RS

-3.5

Varity_R

0.036

gMVP

0.029

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.064

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over